chr1-162249311-C-T

Variant names:

• chr1-162249311-C-T
• rs4656362
• NM_014697.3:c.178-38033C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014697.3(NOS1AP):​c.178-38033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,104 control chromosomes in the GnomAD database, including 2,934 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2934 hom., cov: 32)
• Consequence: NOS1AP NM_014697.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 6 publications found

Genes affected

NOS1AP (HGNC:16859): (nitric oxide synthase 1 adaptor protein) This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

NOS1AP Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 22

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014697.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	NM_014697.3	MANE Select	c.178-38033C>T		intron	N/A	NP_055512.1	O75052-1
	NOS1AP	NM_001164757.2		c.178-38033C>T		intron	N/A	NP_001158229.1	O75052-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS1AP	ENST00000361897.10	TSL:1 MANE Select	c.178-38033C>T		intron	N/A	ENSP00000355133.5	O75052-1
	NOS1AP	ENST00000530878.5	TSL:1	c.178-38033C>T		intron	N/A	ENSP00000431586.1	O75052-3
	NOS1AP	ENST00000430120.3	TSL:1	n.178-38033C>T		intron	N/A	ENSP00000396713.3	E9PSG0

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25592 AN: 151986 Hom.: 2936 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25588 AN: 152104 Hom.: 2934 Cov.: 32 AF XY: 0.179 AC XY: 13311 AN XY: 74328

African (AFR) AF: 0.0388 AC: 1611 AN: 41526

American (AMR) AF: 0.233 AC: 3560 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2519 AN: 5160

South Asian (SAS) AF: 0.312 AC: 1498 AN: 4800

European-Finnish (FIN) AF: 0.256 AC: 2704 AN: 10564

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.182 AC: 12402 AN: 67986

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.127 Hom.: 413

Bravo AF: 0.159

Asia WGS AF: 0.358 AC: 1241 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4656362; hg19: chr1-162219101;